The human immunodeficiency virus type 1 (HIV-1) is the etiological agent of the acquired immunodeficiency syndrome (AIDS) that develops in HIV-1-infected individuals of all ages after a long clinical latent period. HIV-1-infected elder individuals have a shorter AIDS-free period and shorter life expectancy than individuals aged 13-49 years. With the advent of life-prolonging therapies such as anti-retroviral drugs for opportunistic infections, an increase in life expectancy post HIV exposure has been observed worldwide with approximately 580 million HIV-infected subjects over 50 years of age in 1999 compared to approximately 1 billion people expected in 2020. With this increased incidence in aged populations, it is important to determine if AIDS pathology, the HIV infection cycle, and mode of viral transmission are distinct in susceptible cells and/or subjects of differing age groups. Despite the extensive documentation on HIV-1 infectivity, replication within target cells, mechanism(s) of viral immunopathogenesis, and the development of AIDS in adults, no specific cellular- and/or molecular-based studies have been published to date examining any differential infectivity or propagation of HIV-1 within immune cells derived from elderly subjects or within HIV-1-infected elderly patients. Results from our laboratory have demonstrated significant differences in viral growth between young and aged human and primate mononuclear cells. Increased titers of virus were observed in HIV-1-infected aged mononuclear cells and lymphocytes compared to virally infected cells from younger donors. We believe that aged lymphocytes may be less susceptible to HIV-1-mediated cell death and may serve as a reservoir promoting virion production. Given T cell phenotypic alterations that have been observed in various chronic inflammatory disease states and aging, we believe that a similar systemic Th2 polarization may occur in circulating T cells of elderly subjects making them more susceptible to HIV-1 disease. Based on these findings, we are examining various parameters of HIV-1-mediated signaling, replication and immunopathogenesis using young and aged mononuclear cells and T lymphocytes. In addition, two large collaborative clinical trials are currently underway comprised of cohorts of age-, race- and gender-matched control and HIV-infected young and older subjects to assess the in vivo immune and physiological alterations associated with HIV infections in elderly patients. Moreover, additional studies are being performed examining alterations in the circulating homocysteine, vitamin B12, folate, and red blood cell folate levels in these subjects to determine if there are any age- and HIV-related changes in these subjects and any possible correlations with immune phenotypes and cellular apoptosis. Such information should provide invaluable information on any age-related differences in AIDS pathogenesis.